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1. Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells

Author: Suelen Silva Gomes Dias, Tamires Cunha-Fernandes, Luciana Souza-Moreira, Vinicius Cardoso Soares, Giselle Barbosa Lima, Isaclaudia G. Azevedo-Quintanilha, Julia Santos, Filipe Pereira-Dutra, Caroline Freitas, Patricia A. Reis, Stevens Kastrup Rehen, Fernando A. Bozza, Thiago M. Lopes Souza, Cecilia J. G. de Almeida, and Patricia T. Bozza
Subjects: Lipid metabolism, Lipid droplets, Immunometabolism, Inflammation, Zika virus, Neuroinfection, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we show that blocking LD formation has major roles in inflammatory cytokine production in the brain. Moreover, we observed that inhibition of DGAT-1 inhibited the weight loss and mortality induced by ZIKV infection in vivo. Our results reveal that LD biogenesis triggered by ZIKV infection is a crucial step for ZIKV replication and pathogenesis in neural cells. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development.
Published: 2023
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2. A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis

Author: Daniela P. Mendes-de-Almeida, Fernanda S. G. Kehdy, Remy Martins-Gonçalves, Joanna Bokel, Eduarda Grinsztejn, Patrícia Mouta Nunes de Oliveira, Maria de Lourdes de Sousa Maia, Brenda Hoagland, Sandra Wagner Cardoso, Beatriz Grinsztejn, Marilda M. Siqueira, Pedro Kurtz, Patricia T. Bozza, and Cristiana C. Garcia
Subjects: vaccine-induced thrombotic thrombocytopenia, ChAdOx1 nCoV-19 vaccine, genetic predisposition, polymorphisms, anti-PF4 antibodies, VITT, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.
Published: 2023
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3. Acute to post-acute COVID-19 thromboinflammation persistence: Mechanisms and potential consequences

Author: Remy Martins-Gonçalves, Eugenio D. Hottz, and Patricia T. Bozza
Subjects: Post-acute COVID-19 syndrome (PACS), Platelet activation, Hypercoagulability, Thromboinflammation, Specialties of internal medicine, RC581-951
Abstract: Concerns for the long-term effects of COVID-19 infection have grown due to frequently reported persisting symptoms that can affect multiple systems for longer than 4 weeks after initial infection, a condition known as long-COVID-19 or post-acute COVID-19 syndrome (PACS). Even nonhospitalized survivors have an elevated risk for the development of thromboinflammatory-associated events, such as ischemic stroke and heart failure, pulmonary embolism and deep vein thrombosis. Recent findings point to the persistence of many mechanisms of hypercoagulability identified to be associated with disease severity and mortality in the acute phase of the disease, such as sustained inflammation and endotheliopathy, accompanied by abnormal fibrin generation and impaired fibrinolysis. Platelets seem to be central to the sustained hypercoagulable state, displaying hyperreactivity to stimuli and increased adhesive capacity. Platelets also contribute to elevated levels of thromboinflammatory mediators and pro-coagulant extracellular vesicles in individuals with ongoing PACS. Despite new advances in the understanding of mechanisms sustaining thromboinflammation in PACS, little is known about what triggers this persistence. In this graphical review, we provide a schematic representation of the known mechanisms and consequences of persisting thromboinflammation in COVID-19 survivors and summarize the hypothesized triggers maintaining this prothrombotic state.
Published: 2023
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4. Increased platelet activation and platelet-inflammasome engagement during chikungunya infection

Author: Isaclaudia Gomes de Azevedo-Quintanilha, Mariana Macedo Campos, Ana Paula Teixeira Monteiro, Alessandra Dantas do Nascimento, Andrea Surrage Calheiros, Douglas Mathias Oliveira, Suelen Silva Gomes Dias, Vinicius Cardoso Soares, Julia da Cunha Santos, Isabel Tavares, Thiago Moreno Lopes Souza, Eugenio D. Hottz, Fernando A. Bozza, and Patricia T. Bozza
Subjects: platelets, activation, chikungunya, inflammatory mediator, inflammasome, Immunologic diseases. Allergy, RC581-607
Abstract: Chikungunya fever is a viral disease transmitted by mosquitoes of the genus Aedes. The infection is usually symptomatic and most common symptoms are fever accompanied by joint pain and swelling. In most cases symptoms subside within a week. However, severe prolonged and disabling joint pain, that may persist for several months, even years, are reported. Although the pathogenesis of Chikungunya infection is not fully understood, the evolution to severe disease seems to be associated with the activation of immune mechanisms and the action of inflammatory mediators. Platelets are recognized as inflammatory cells with fundamental activities in the immune response, maintenance of vascular stability and pathogenicity of several inflammatory and infectious diseases. Although the involvement of platelets in the pathogenesis of viral diseases has gained attention in recent years, their activation in Chikungunya has not been explored. The aim of this study was to analyze platelet activation and the possible role of platelets in the amplification of the inflammatory response during Chikungunya infection. We prospectively included 132 patients attended at the Quinta D’Or hospital and 25 healthy volunteers during the 2016 epidemic in Rio de Janeiro, Brazil. We observed increased expression of CD62P on the surface of platelets, as well as increased plasma levels of CD62P and platelet-derived inflammatory mediators indicating that the Chikungunya infection leads to platelet activation. In addition, platelets from chikungunya patients exhibit increased expression of NLRP3, caspase 4, and cleaved IL-1β, suggestive of platelet-inflammasome engagement during chikungunya infection. In vitro experiments confirmed that the Chikungunya virus directly activates platelets. Moreover, we observed that platelet activation and soluble p-selectin at the onset of symptoms were associated with development of chronic forms of the disease. Collectively, our data suggest platelet involvement in the immune processes and inflammatory amplification triggered by the infection.
Published: 2022
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5. Proteomic Profile of Procoagulant Extracellular Vesicles Reflects Complement System Activation and Platelet Hyperreactivity of Patients with Severe COVID-19

Author: Emilly Caroline dos Santos Moraes, Remy Martins-Gonçalves, Luana Rocha da Silva, Samuel Coelho Mandacaru, Reynaldo Magalhães Melo, Isaclaudia Azevedo-Quintanilha, Jonas Perales, Fernando A. Bozza, Thiago Moreno Lopes Souza, Hugo Caire Castro-Faria-Neto, Eugenio D. Hottz, Patricia T. Bozza, and Monique R. O. Trugilho
Subjects: Extracellular vesicles, LC-MS/MS, proteome, SARS-CoV-2, platelets, complement factors, Microbiology, QR1-502
Abstract: BackgroundExtracellular vesicles (EVs) are a valuable source of biomarkers and display the pathophysiological status of various diseases. In COVID-19, EVs have been explored in several studies for their ability to reflect molecular changes caused by SARS-CoV-2. Here we provide insights into the roles of EVs in pathological processes associated with the progression and severity of COVID-19.MethodsIn this study, we used a label-free shotgun proteomic approach to identify and quantify alterations in EV protein abundance in severe COVID-19 patients. We isolated plasma extracellular vesicles from healthy donors and patients with severe COVID-19 by size exclusion chromatography (SEC). Then, flow cytometry was performed to assess the origin of EVs and to investigate the presence of circulating procoagulant EVs in COVID-19 patients. A total protein extraction was performed, and samples were analyzed by nLC-MS/MS in a Q-Exactive HF-X. Finally, computational analysis was applied to signify biological processes related to disease pathogenesis.ResultsWe report significant changes in the proteome of EVs from patients with severe COVID-19. Flow cytometry experiments indicated an increase in total circulating EVs and with tissue factor (TF) dependent procoagulant activity. Differentially expressed proteins in the disease groups were associated with complement and coagulation cascades, platelet degranulation, and acute inflammatory response.ConclusionsThe proteomic data reinforce the changes in the proteome of extracellular vesicles from patients infected with SARS-CoV-2 and suggest a role for EVs in severe COVID-19.
Published: 2022
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6. Haem oxygenase protects against thrombocytopaenia and malaria-associated lung injury

Author: Isaclaudia G. de Azevedo-Quintanilha, Isabel M. Medeiros-de-Moraes, André C. Ferreira, Patrícia A. Reis, Adriana Vieira-de-Abreu, Robert A. Campbell, Andrew S. Weyrich, Patricia T. Bozza, Guy A. Zimmerman, and Hugo C. Castro-Faria-Neto
Subjects: Acute lung injury, Acute respiratory distress syndrome, Inflammation, Malaria, Platelets, Heme oxygenase 1, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Malaria-triggered lung injury can occur in both severe and non-severe cases. Platelets may interact with parasitized erythrocytes, leukocytes and endothelium. These interactions can lead to microvessel obstructions and induce release of inflammatory mediators. Induction of the haem oxygenase enzyme is important in the host’s response to free haem and to several other molecules generated by infectious or non-infectious diseases. In addition, an important role for the haem oxygenase-1 isotype has been demonstrated in experimental cerebral malaria and in clinical cases. Therefore, the present work aims to determine the influence of haem oxygenase in thrombocytopaenia and acute pulmonary injury during infection with Plasmodium berghei strain NK65. Methods C57BL/6 mice were infected with P. berghei and analysed 7-10 days post-infection. For each experiment, Cobalt Protoporphyrin IX/CoPPIX or saline were administered. Bronchoalveolar lavage fluid was used for total and differential leukocyte count and for protein measurement. Lungs were used for histological analyses or for analysis of cytokines and western blotting. The lung permeability was analysed by Evans blue dye concentration. Platelet-leukocyte aggregate formation was assayed using the flow cytometer. Results Plasmodium berghei NK65 infection generated an intense lung injury, with increased levels of inflammatory mediators, oedema, and cell migration into the lung. Plasmodium berghei infection was also accompanied by marked thrombocytopaenia and formation of platelet-leukocyte aggregates in peripheral blood. Treatment with the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) modified the inflammatory response but did not affect the evolution of parasitaemia. Animals treated with CoPPIX showed an improvement in lung injury, with decreased inflammatory infiltrate in the lung parenchyma, oedema and reduced thrombocytopaenia. Conclusion Data here presented suggest that treatment with CoPPIX inducer leads to less severe pulmonary lung injury and thrombocytopaenia during malaria infection, thus increasing animal survival.
Published: 2020
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7. Simvastatin Downregulates the SARS-CoV-2-Induced Inflammatory Response and Impairs Viral Infection Through Disruption of Lipid Rafts

Author: Lívia Teixeira, Jairo R. Temerozo, Filipe S. Pereira-Dutra, André Costa Ferreira, Mayara Mattos, Barbara Simonson Gonçalves, Carolina Q. Sacramento, Lohanna Palhinha, Tamires Cunha-Fernandes, Suelen S. G. Dias, Vinicius Cardoso Soares, Ester A. Barreto, Daniella Cesar-Silva, Natalia Fintelman-Rodrigues, Camila R. R. Pão, Caroline S. de Freitas, Patrícia A. Reis, Eugenio D. Hottz, Fernando A. Bozza, Dumith C. Bou-Habib, Elvira M. Saraiva, Cecília J. G. de Almeida, João P. B. Viola, Thiago Moreno L. Souza, and Patricia T. Bozza
Subjects: statin, COVID-19, inflammation, lipid rafts, SARS-CoV-2, Immunologic diseases. Allergy, RC581-607
Abstract: Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In observational clinical studies, statins have been identified as beneficial to hospitalized patients with COVID-19. However, experimental evidence of underlying statins protection against SARS-CoV-2 remains elusive. Here we reported for the first-time experimental evidence of the protective effects of simvastatin treatment both in vitro and in vivo. We found that treatment with simvastatin significantly reduced the viral replication and lung damage in vivo, delaying SARS-CoV-2-associated physiopathology and mortality in the K18-hACE2-transgenic mice model. Moreover, simvastatin also downregulated the inflammation triggered by SARS-CoV-2 infection in pulmonary tissue and in human neutrophils, peripheral blood monocytes, and lung epithelial Calu-3 cells in vitro, showing its potential to modulate the inflammatory response both at the site of infection and systemically. Additionally, we also observed that simvastatin affected the course of SARS-CoV-2 infection through displacing ACE2 on cell membrane lipid rafts. In conclusion, our results show that simvastatin exhibits early protective effects on SARS-CoV-2 infection by inhibiting virus cell entry and inflammatory cytokine production, through mechanisms at least in part dependent on lipid rafts disruption.
Published: 2022
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8. Effect of Convalescent Plasma in Critically Ill Patients With COVID-19: An Observational Study

Author: Pedro Kurtz, Cassia Righy, Monica Gadelha, Fernando A. Bozza, Patricia T. Bozza, Bruno Gonçalves, Leonardo S. L. Bastos, Andre M. Vale, Luiza M. Higa, Leda Castilho, Fabio L. Monteiro, Nestor Charris, Fernanda Fialho, Ricardo Turon, Alexandro Guterres, Renan Lyra Miranda, Carlos Henrique de Azeredo Lima, Vanessa de Caro, Marco Aurelio Prazeres, Nina Ventura, Clara Gaspari, Fabio Miranda, Paulo Jose da Mata, Margarida Pêcego, Sheila Mateos, Maria Esther Lopes, Shirley Castilho, Álvaro Oliveira, Carla Boquimpani, Andréa Rabello, Josiane Lopes, Orlando Conceição Neto, Orlando da C. Ferreira, Amilcar Tanuri, Paulo Niemeyer Filho, and Luiz Amorim
Subjects: convalescent plasma, coronavirus, acute respiratory distress syndrome, COVID-19, survival, Medicine (General), R5-920
Abstract: Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19.Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan–Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed.Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48–68), disease duration was 10 days (IQR 6–13), and 86% were mechanically ventilated. At least 29 out of 41CP-recipients had baseline IgG titers ≥ 1:1,080. Clinical improvement within 28 days occurred in 19 (46%) CP-treated patients, as compared to 23 (32%) in the SOC group [adjusted hazard ratio (aHR) 0.91 (0.49–1.69)]. There was no significant change in 28-day mortality (CP 49% vs. SOC 56%; aHR 0.90 [0.52–1.57]). Biomarker assessment revealed reduced inflammatory activity and increased lymphocyte count after CP.Conclusions: In this study, CP was not associated with clinical improvement or increase in 28-day survival. However, our study may have been underpowered and included patients with high IgG titers and life-threatening disease.Clinical Trial Registration: The study protocol was retrospectively registered at the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-4vm3yy (http://www.ensaiosclinicos.gov.br).
Published: 2021
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9. Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

Author: Natália R. T. Amorim, Glaucia Souza-Almeida, Tatiana Luna-Gomes, Patricia T. Bozza, Claudio Canetti, Bruno L. Diaz, Clarissa M. Maya-Monteiro, and Christianne Bandeira-Melo
Subjects: eosinophils, mast cells, lipid droplets, leptin, prostaglandin D2, leukotriene C4, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Eosinophils are key regulators of adipose tissue homeostasis, thus characterization of adipose tissue-related molecular factors capable of regulating eosinophil activity is of great interest. Leptin is known to directly activate eosinophils in vitro, but leptin ability of inducing in vivo eosinophilic inflammatory response remains elusive. Here, we show that leptin elicits eosinophil influx as well as its activation, characterized by increased lipid body biogenesis and LTC4 synthesis. Such leptin-triggered eosinophilic inflammatory response was shown to be dependent on activation of the mTOR signaling pathway, since it was (i) inhibited by rapamycin pre-treatment and (ii) reduced in PI3K-deficient mice. Local infiltration of activated eosinophils within leptin-driven inflammatory site was preceded by increased levels of classical mast cell-derived molecules, including TNFα, CCL5 (RANTES), and PGD2. Thus, mice were pre-treated with a mast cell degranulating agent compound 48/80 which was capable to impair leptin-induced PGD2 release, as well as eosinophil recruitment and activation. In agreement with an indirect mast cell-driven phenomenon, eosinophil accumulation induced by leptin was abolished in TNFR-1 deficient and also in HQL-79–pretreated mice, but not in mice pretreated with neutralizing antibodies against CCL5, indicating that both typical mast cell-driven signals TNFα and PGD2, but not CCL5, contribute to leptin-induced eosinophil influx. Distinctly, leptin-induced eosinophil lipid body (lipid droplet) assembly and LTC4 synthesis appears to depend on both PGD2 and CCL5, since both HQL-79 and anti-CCL5 treatments were able to inhibit these eosinophil activation markers. Altogether, our data show that leptin triggers eosinophilic inflammation in vivo via an indirect mechanism dependent on activation of resident mast cell secretory activity and mediation by TNFα, CCL5, and specially PGD2.
Published: 2020
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10. SARS-CoV-2: Ultrastructural Characterization of Morphogenesis in an In Vitro System

Author: Debora Ferreira Barreto-Vieira, Marcos Alexandre Nunes da Silva, Ana Luisa Teixeira de Almeida, Arthur da Costa Rasinhas, Maria Eduarda Monteiro, Milene Dias Miranda, Fernando Couto Motta, Marilda M. Siqueira, Wendell Girard-Dias, Bráulio Soares Archanjo, Patricia T. Bozza, Thiago Moreno L. Souza, Suelen Silva Gomes Dias, Vinicius Cardoso Soares, and Ortrud Monika Barth
Subjects: SARS-CoV-2, Vero-E6 cells, ultrastructural studies, morphogenesis, transmission electron microscopy, scanning electron microscopy, Microbiology, QR1-502
Abstract: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impacted public health and the world economy and fueled a worldwide race to approve therapeutic and prophylactic agents, but so far there are no specific antiviral drugs. Understanding the biology of the virus is the first step in structuring strategies to combat it, and in this context several studies have been conducted with the aim of understanding the replication mechanism of SARS-CoV-2 in vitro systems. In this work, studies using transmission and scanning electron microscopy and 3D electron microscopy modeling were performed with the goal of characterizing the morphogenesis of SARS-CoV-2 in Vero-E6 cells. Several ultrastructural changes were observed—such as syncytia formation, cytoplasmic membrane projections, lipid droplets accumulation, proliferation of double-membrane vesicles derived from the rough endoplasmic reticulum, and alteration of mitochondria. The entry of the virus into cells occurred through endocytosis. Viral particles were observed attached to the cell membrane and in various cellular compartments, and extrusion of viral progeny took place by exocytosis. These findings allow us to infer that Vero-E6 cells are highly susceptible to SARS-CoV-2 infection as described in the literature and their replication cycle is similar to that described with SARS-CoV and MERS-CoV in vitro models.
Published: 2022
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11. Schistosomal Lipids Activate Human Eosinophils via Toll-Like Receptor 2 and PGD2 Receptors: 15-LO Role in Cytokine Secretion

Author: Kelly G. Magalhães, Tatiana Luna-Gomes, Fabio Mesquita-Santos, Rafael Corrêa, Leonardo Santos Assunção, Georgia Correa Atella, Peter F. Weller, Christianne Bandeira-Melo, and Patricia T. Bozza
Subjects: eosinophil, PGD2, lipids, schistosoma, TLR, LPC, Immunologic diseases. Allergy, RC581-607
Abstract: Parasite-derived lipids may play important roles in host-pathogen interactions and immune evasion mechanisms. Remarkable accumulation of eosinophils is a characteristic feature of inflammation associated with parasitic disease, especially caused by helminthes. Infiltrating eosinophils are implicated in the pathogenesis of helminth infection by virtue of their capacity to release an array of tissue-damaging and immunoregulatory mediators. However, the mechanisms involved in the activation of human eosinophils by parasite-derived molecules are not clear. Here we investigated the effects and mechanisms of schistosomal lipids-induced activation of human eosinophils. Our results showed that stimulation of human eosinophils in vitro with total lipid extracts from adult worms of S. mansoni induced direct activation of human eosinophils, eliciting lipid droplet biogenesis, synthesis of leukotriene (LT) C4 and eoxin (EX) C4 (14,15 LTC4) and secretion of eosinophil pre-formed TGFβ. We demonstrated that main eosinophil activating components within S. mansoni lipid extract are schistosomal-derived lysophosphatidylcholine (LPC) and prostaglandin (PG)D2. Moreover, TLR2 is up-regulated in human eosinophils upon stimulation with schistosomal lipids and pre-treatment with anti-TLR2 inhibited both schistosomal lipids- and LPC-, but not PGD2-, induced lipid droplet biogenesis and EXC4 synthesis within eosinophils, indicating that TLR2 mediates LPC-driven human eosinophil activation. By employing PGD2 receptor antagonists, we demonstrated that DP1 receptors are also involved in various parameters of human eosinophil activation induced by schistosomal lipids, but not by schistosomal LPC. In addition, schistosomal lipids and their active components PGD2 and LPC, triggered 15-LO dependent production of EXC4 and secretion of TGFβ. Taken together, our results showed that schistosomal lipids contain at least two components—LPC and PGD2—that are capable of direct activation of human eosinophils acting on distinct eosinophil-expressed receptors, noticeably TLR2 as well as DP1, trigger human eosinophil activation characterized by production/secretion of pro-inflammatory and immunoregulatory mediators.
Published: 2019
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12. Lipid droplet levels vary heterogeneously in response to simulated gastrointestinal stresses in different probiotic Saccharomyces cerevisiae strains

Author: Daniel Zamith-Miranda, Mariana L. Palma, Gabriel S. Matos, Johnathon G. Schiebel, Clarissa M. Maya-Monteiro, Marcos Aronovich, Patricia T. Bozza, Fernando A. Bozza, Leonardo Nimrichter, Monica Montero-Lomeli, Ernesto T.A. Marques, Jr, Flaviano S. Martins, and Bruno Douradinha
Subjects: Saccharomyces cerevisiae var boulardii, Saccharomyces cerevisiae, Probiotics, Lipid droplets, Gastrointestinal tract stresses, Stress resistance, Nutrition. Foods and food supply, TX341-641
Abstract: To exert their therapeutic action, probiotic Saccharomyces cerevisiae strains must survive harsh digestive environments. Lipid droplets accumulate in cells which undergo stress-inducing situations, supposedly having a protective role. We assessed lipid droplet levels, either naturally accumulated or induced in response to digestive challenges, of probiotic strains S. boulardii, S. cerevisiae A-905, S. cerevisiae Sc47 and S. cerevisiae L11, and of non-probiotic strains S. cerevisiae BY4741 and S. cerevisiae BY4743. Strains 905 and Sc47 had lower and higher lipid droplet levels, respectively, when compared to the remaining strains, showing that higher accumulationof these neutral lipids is not a feature shared by all probiotic Saccharomyces strains. When submitted to simulated gastric or bile salts environments, lipid droplet levels increase in all tested probiotic strains, at least for one to the induced stresses, suggesting that lipid droplets participate in the protective mechanisms against gastrointestinal stresses in probiotic Saccharomyces yeasts.
Published: 2016
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13. Lipids From Trypanosoma cruzi Amastigotes of RA and K98 Strains Generate a Pro-inflammatory Response via TLR2/6

Author: Emanuel Bott, Alan B. Carneiro, Guadalupe Gimenez, María G. López, Estela M. Lammel, Georgia C. Atella, Patricia T. Bozza, and María L. Belaunzarán
Subjects: Trypanosoma cruzi, lipids, phospholipase A1, pro-inflammatory, TLR2/6, Microbiology, QR1-502
Abstract: Lipids from microorganisms are ligands of Toll like receptors (TLRs) and modulate the innate immune response. Herein, we analyze in vitro the effect of total lipid extracts from Trypanosoma cruzi amastigotes of RA and K98 strains (with polar biological behavior) on the induction of the inflammatory response and the involvement of TLRs in this process. We demonstrated that total lipid extracts from both strains induced lipid body formation, cyclooxygenase-2 expression and TNF-α and nitric oxide release in macrophages, as well as NF-κB activation and IL-8 release in HEK cells specifically through a TLR2/6 dependent pathway. We also evaluated the inflammatory response induced by total lipid extracts obtained from lysed parasites that were overnight incubated to allow the action of parasite hydrolytic enzymes, such as Phospholipase A1, over endogenous phospholipids. After incubation, these total lipid extracts showed a significantly reduced pro-inflammatory response, which could be attributed to the changes in the content of known bioactive lipid molecules like lysophospholipids and fatty acids, here reported. Moreover, analyses of total fatty acids in each lipid extract were performed by gas chromatography-mass spectrometry. Our results indicate a relevant role of T. cruzi lipids in the induction of a pro-inflammatory response through the TLR2/6 pathway that could contribute to the modulation of the immune response and host survival.
Published: 2018
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14. Lipid Droplet, a Key Player in Host-Parasite Interactions

Author: Adriana Lima Vallochi, Livia Teixeira, Karina da Silva Oliveira, Clarissa Menezes Maya-Monteiro, and Patricia T. Bozza
Subjects: lipid droplets, lipid bodies, parasite, intracellular pathogen, eicosanoids, inflammation, Immunologic diseases. Allergy, RC581-607
Abstract: Lipid droplets (lipid bodies, LDs) are dynamic organelles that have important roles in regulating lipid metabolism, energy homeostasis, cell signaling, membrane trafficking, and inflammation. LD biogenesis, composition, and functions are highly regulated and may vary according to the stimuli, cell type, activation state, and inflammatory environment. Increased cytoplasmic LDs are frequently observed in leukocytes and other cells in a number of infectious diseases. Accumulating evidence reveals LDs participation in fundamental mechanisms of host-pathogen interactions, including cell signaling and immunity. LDs are sources of eicosanoid production, and may participate in different aspects of innate signaling and antigen presentation. In addition, intracellular pathogens evolved mechanisms to subvert host metabolism and may use host LDs, as ways of immune evasion and nutrients source. Here, we review mechanisms of LDs biogenesis and their contributions to the infection progress, and discuss the latest discoveries on mechanisms and pathways involving LDs roles as regulators of the immune response to protozoan infection.
Published: 2018
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15. Leptin Mediates In Vivo Neutrophil Migration: Involvement of Tumor Necrosis Factor-Alpha and CXCL1

Author: Glaucia Souza-Almeida, Heloisa D’Avila, Patricia E. Almeida, Tatiana Luna-Gomes, Sally Liechocki, Barbara Walzog, Ingrid Hepper, Hugo Caire Castro-Faria-Neto, Patricia T. Bozza, Christianne Bandeira-Melo, and Clarissa M. Maya-Monteiro
Subjects: leptin, neutrophil, inflammation, tumor necrosis factor-alpha, CXCL1, leukotriene B4, Immunologic diseases. Allergy, RC581-607
Abstract: Leptin directly activates macrophages and lymphocytes, but the role of leptin in neutrophil activation and migration is still controversial. Here, we investigate the in vivo mechanisms of neutrophil migration induced by leptin. The intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration-dependent neutrophil influx. We did not observe the enhancement of lipid bodies/droplets in neutrophils, after leptin treatment, as we had observed previously in peritoneal macrophages. The participation of leukotriene B4 (LTB4) in neutrophil recruitment triggered by leptin was investigated using different strategies. Leptin-induced neutrophil recruitment occurs both in the absence of 5-lipoxygenase activity in 5-lipoxygenase (5-LO)−/− mice and after the administration of either 5-LO inhibitor (Zileuton) or the LTB4 receptor antagonist (U-75302). Moreover, no direct induction of LTB4 by leptin could be observed. Neutrophil influx could not be prevented by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, contrasting with the leptin-induced signaling for lipid body formation in macrophage that is mTOR-dependent. Leptin administration led to tumor necrosis factor-alpha (TNFα) production by the peritoneal cells both in vivo and in vitro. In addition, neutrophil recruitment was inhibited in tumor necrosis factor receptor 1 (TNFR1−/−) mice, indicating a role for TNF in leptin-induced neutrophil recruitment to the peritoneal cavity. Leptin-induced neutrophil influx was PI3Kγ-dependent, as it was absent in PI3Kγ−/− mice. Accordingly, leptin induced the peritoneal cells to produce CXCL1, both in vivo and in vitro, and the neutrophil influx was ablated after using an antibody against CXCL1. Our results establish TNFα/TNFR1- and CXCL1-dependent signaling as important pathways for leptin-induced neutrophil migration in vivo.
Published: 2018
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16. PPARγ Expression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

Author: Patricia E. Almeida, Alan Brito Carneiro, Adriana R. Silva, and Patricia T. Bozza
Subjects: Biology (General), QH301-705.5
Abstract: Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control. Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPARγ) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγ during mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγ expression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγ expression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγ expression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγ expression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγ enhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγ in favoring the establishment of chronic infection. Collectively, PPARγ is emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.
Published: 2012
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17. Persisting Platelet Activation and Hyperactivity in COVID-19 Survivors

Author: Remy Martins-Gonçalves, Mariana M. Campos, Lohanna Palhinha, Isaclaudia G. Azevedo-Quintanilha, Mayara Abud Mendes, Jairo Ramos Temerozo, Júlia Toledo-Mendes, Paulo H. Rosado-de-Castro, Fernando A. Bozza, Rosana Souza Rodrigues, Eugenio D. Hottz, and Patricia T. Bozza
Subjects: Blood Platelets, SARS-CoV-2, Physiology, Humans, COVID-19, Survivors, Platelet Activation, Cardiology and Cardiovascular Medicine
Published: 2022

18. Increased Lung Immune Metabolic Activity in COVID-19 Survivors

Author: Rosana Souza Rodrigues, Gabriel Motta Ribeiro, Miriam Menna Barreto, Walter Araujo Zin, Júlia de Toledo-Mendes, Philippe Alcantara G. Martins, Sergio Altino de Almeida, Rodrigo Basílio, Remy Martins-Gonçalves, Eugênio Damaceno Hottz, Patricia T. Bozza, Fernando A. Bozza, Alysson Roncally Silva Carvalho, and Paulo Henrique Rosado-de-Castro
Subjects: Adult, Male, Inflammation, COVID-19, Thrombosis, General Medicine, Pneumonia, Middle Aged, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Humans, Radiology, Nuclear Medicine and imaging, Female, Survivors, Lung, Biomarkers
Abstract: We quantified lung glycolytic metabolic activity, clinical symptoms and inflammation, coagulation, and endothelial activation biomarkers in 2019 coronavirus disease (COVID-19) pneumonia survivors.Adults previously hospitalized with moderate to severe COVID-19 pneumonia were prospectively included. Subjects filled out a questionnaire on clinical consequences, underwent chest CT and 18 F-FDG PET/CT, and provided blood samples on the same day. Forty-five volunteers served as control subjects. Analysis of CT images and quantitative voxel-based analysis of PET/CT images were performed for both groups. 18 F-FDG uptake in the whole-lung volume and in high- and low-attenuation areas was calculated and normalized to liver values. Quantification of plasma markers of inflammation (interleukin 6), d -dimer, and endothelial cell activation (angiopoietins 1 and 2, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) was also performed.We enrolled 53 COVID-19 survivors (62.3% were male; median age, 50 years). All survivors reported at least 1 persistent symptom, and 41.5% reported more than 6 symptoms. The mean lung density was greater in survivors than in control subjects, and more metabolic activity was observed in normal and dense lung areas, even months after symptom onset. Plasma proinflammatory, coagulation, and endothelial activation biomarker concentrations were also significantly higher in survivors.We observed more metabolic activity in areas of high and normal lung attenuation several months after moderate to severe COVID-19 pneumonia. In addition, plasma markers of thromboinflammation and endothelial activation persisted. These findings may have implications for our understanding of the in vivo pathogenesis and long-lasting effects of COVID-19 pneumonia.
Published: 2022

19. Apixaban, an orally available anticoagulant, inhibits SARS-CoV-2 replication and its major protease in a non-competitive way

Author: Otávio Augusto Chaves, Carolina Q Sacramento, Natalia Fintelman-Rodrigues, Jairo Ramos Temerozo, Filipe Pereira-Dutra, Daniella M Mizurini, Robson Q Monteiro, Leonardo Vazquez, Patricia T Bozza, Hugo Caire Castro-Faria-Neto, and Thiago Moreno L Souza
Subjects: Pyridones, SARS-CoV-2, Genetics, Anticoagulants, Humans, Pyrazoles, Cell Biology, General Medicine, Molecular Biology, Peptide Hydrolases, COVID-19 Drug Treatment
Published: 2022

20. Prevention of lipid droplet accumulation by DGAT1 inhibition ameliorates sepsis-induced liver injury and inflammation

Author: Lívia Teixeira, Filipe S. Pereira-Dutra, Patrícia A. Reis, Tamires Cunha-Fernandes, Marcos Y. Yoshinaga, Luciana Souza-Moreira, Ellen K. Souza, Ester A. Barreto, Thiago P. Silva, Hugo Espinheira-Silva, Tathiany Igreja, Maísa M. Antunes, Ana Cristina S. Bombaça, Cassiano F. Gonçalves-de-Albuquerque, Gustavo B. Menezes, Eugênio D. Hottz, Rubem F.S. Menna-Barreto, Clarissa M. Maya-Monteiro, Fernando A. Bozza, Sayuri Miyamoto, Rossana C.N. Melo, and Patrícia T. Bozza
Subjects: immunometabolism, inflammation, sepsis, MODS, steatosis, lipid peroxidation, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Lipid droplet (LD) accumulation in cells and tissues is understood to be an evolutionarily conserved tissue tolerance mechanism to prevent lipotoxicity caused by excess lipids; however, the presence of excess LDs has been associated with numerous diseases. Sepsis triggers the reprogramming of lipid metabolism and LD accumulation in cells and tissues, including the liver. The functions and consequences of sepsis-triggered liver LD accumulation are not well known. Methods: Experimental sepsis was induced by CLP (caecal ligation and puncture) in mice. Markers of hepatic steatosis, liver injury, hepatic oxidative stress, and inflammation were analysed using a combination of functional, imaging, lipidomic, protein expression and immune-enzymatic assays. To prevent LD formation, mice were treated orally with A922500, a pharmacological inhibitor of DGAT1. Results: We identified that liver LD overload correlates with liver injury and sepsis severity. Moreover, the progression of steatosis from 24 h to 48 h post-CLP occurs in parallel with increased cytokine expression, inflammatory cell recruitment and oxidative stress. Lipidomic analysis of purified LDs demonstrated that sepsis leads LDs to harbour increased amounts of unsaturated fatty acids, mostly 18:1 and 18:2. An increased content of lipoperoxides within LDs was also observed. Conversely, the impairment of LD formation by inhibition of the DGAT1 enzyme reduces levels of hepatic inflammation and lipid peroxidation markers and ameliorates sepsis-induced liver injury. Conclusions: Our results indicate that sepsis triggers lipid metabolism alterations that culminate in increased liver LD accumulation. Increased LDs are associated with disease severity and liver injury. Moreover, inhibition of LD accumulation decreased the production of inflammatory mediators and lipid peroxidation while improving tissue function, suggesting that LDs contribute to the pathogenesis of liver injury triggered by sepsis. Impact and Implications: Sepsis is a complex life-threatening syndrome caused by dysregulated inflammatory and metabolic host responses to infection. The observation that lipid droplets may contribute to sepsis-associated organ injury by amplifying lipid peroxidation and inflammation provides a rationale for therapeutically targeting lipid droplets and lipid metabolism in sepsis.
Published: 2024
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21. Leptin Mediates

Author: Glaucia, Souza-Almeida, Heloisa, D'Avila, Patricia E, Almeida, Tatiana, Luna-Gomes, Sally, Liechocki, Barbara, Walzog, Ingrid, Hepper, Hugo Caire, Castro-Faria-Neto, Patricia T, Bozza, Christianne, Bandeira-Melo, and Clarissa M, Maya-Monteiro
Subjects: Leptin, Male, Mice, Knockout, Mice, Inbred C3H, Arachidonate 5-Lipoxygenase, Neutrophils, Tumor Necrosis Factor-alpha, Chemokine CXCL1, digestive, oral, and skin physiology, Immunology, neutrophil, leukotriene B4, CXCL1, Mice, Inbred C57BL, Phosphatidylinositol 3-Kinases, Neutrophil Infiltration, Cell Movement, Receptors, Tumor Necrosis Factor, Type I, inflammation, Macrophages, Peritoneal, Animals, hormones, hormone substitutes, and hormone antagonists, Chemokine CCL3, Original Research
Abstract: Leptin directly activates macrophages and lymphocytes, but the role of leptin in neutrophil activation and migration is still controversial. Here, we investigate the in vivo mechanisms of neutrophil migration induced by leptin. The intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration-dependent neutrophil influx. We did not observe the enhancement of lipid bodies/droplets in neutrophils, after leptin treatment, as we had observed previously in peritoneal macrophages. The participation of leukotriene B4 (LTB4) in neutrophil recruitment triggered by leptin was investigated using different strategies. Leptin-induced neutrophil recruitment occurs both in the absence of 5-lipoxygenase activity in 5-lipoxygenase (5-LO)−/− mice and after the administration of either 5-LO inhibitor (Zileuton) or the LTB4 receptor antagonist (U-75302). Moreover, no direct induction of LTB4 by leptin could be observed. Neutrophil influx could not be prevented by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, contrasting with the leptin-induced signaling for lipid body formation in macrophage that is mTOR-dependent. Leptin administration led to tumor necrosis factor-alpha (TNFα) production by the peritoneal cells both in vivo and in vitro. In addition, neutrophil recruitment was inhibited in tumor necrosis factor receptor 1 (TNFR1−/−) mice, indicating a role for TNF in leptin-induced neutrophil recruitment to the peritoneal cavity. Leptin-induced neutrophil influx was PI3Kγ-dependent, as it was absent in PI3Kγ−/− mice. Accordingly, leptin induced the peritoneal cells to produce CXCL1, both in vivo and in vitro, and the neutrophil influx was ablated after using an antibody against CXCL1. Our results establish TNFα/TNFR1- and CXCL1-dependent signaling as important pathways for leptin-induced neutrophil migration in vivo.
Published: 2017

22. Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation

Author: Thiago Moreno L. Souza, Vagner D. Pinho, Cristina F. Setim, Carolina Q. Sacramento, Rodrigo Marcon, Natalia Fintelman-Rodrigues, Otavio A. Chaves, Melina Heller, Jairo R. Temerozo, André C. Ferreira, Mayara Mattos, Patrícia B. Momo, Suelen S. G. Dias, João S. M. Gesto, Filipe Pereira-Dutra, João P. B. Viola, Celso Martins Queiroz-Junior, Lays Cordeiro Guimarães, Ian Meira Chaves, Pedro Pires Goulart Guimarães, Vivian Vasconcelos Costa, Mauro Martins Teixeira, Dumith Chequer Bou-Habib, Patrícia T. Bozza, Anderson R. Aguillón, Jarbas Siqueira-Junior, Sergio Macedo-Junior, Edineia L. Andrade, Guilherme P. Fadanni, Sara E. L. Tolouei, Francine B. Potrich, Adara A. Santos, Naiani F. Marques, João B. Calixto, and Jaime A. Rabi
Subjects: Science
Abstract: The search for antivirals against SARS-CoV-2 continue due to the emergence of variants of concerns, able to escape the vaccinal humoral response. In this work, authors pre-clinically explore the potential of kinetin against SARS-CoV-2, which could be used alone or in combination with other antivirals.
Published: 2023
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23. Platelet proteome reveals features of cell death, antiviral response and viral replication in covid-19

Author: Monique R. O. Trugilho, Isaclaudia G. Azevedo-Quintanilha, João S. M. Gesto, Emilly Caroline S. Moraes, Samuel C. Mandacaru, Mariana M. Campos, Douglas M. Oliveira, Suelen S. G. Dias, Viviane A. Bastos, Marlon D. M. Santos, Paulo C. Carvalho, Richard H. Valente, Eugenio D. Hottz, Fernando A. Bozza, Thiago Moreno L. Souza, Jonas Perales, and Patrícia T. Bozza
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract: Abstract Coronavirus disease 2019 (COVID-19) has affected over 400 million people worldwide, leading to 6 million deaths. Among the complex symptomatology of COVID-19, hypercoagulation and thrombosis have been described to directly contribute to lethality, pointing out platelets as an important SARS-CoV-2 target. In this work, we explored the platelet proteome of COVID-19 patients through a label-free shotgun proteomics approach to identify platelet responses to infection, as well as validation experiments in a larger patient cohort. Exclusively detected proteins (EPs) and differentially expressed proteins (DEPs) were identified in the proteomic dataset and thus classified into biological processes to map pathways correlated with pathogenesis. Significant changes in the expression of proteins related to platelet activation, cell death, and antiviral response through interferon type-I were found in all patients. Since the outcome of COVID-19 varies highly among individuals, we also performed a cross-comparison of proteins found in survivors and nonsurvivors. Proteins belonging to the translation pathway were strongly highlighted in the nonsurvivor group. Moreover, the SARS-CoV-2 genome was fully sequenced in platelets from five patients, indicating viral internalization and preprocessing, with CD147 as a potential entry route. In summary, platelets play a significant role in COVID-19 pathogenesis via platelet activation, antiviral response, and disease severity.
Published: 2022
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24. Human endogenous retrovirus K in the respiratory tract is associated with COVID-19 physiopathology

Author: Jairo R. Temerozo, Natalia Fintelman-Rodrigues, Monique Cristina dos Santos, Eugenio D. Hottz, Carolina Q. Sacramento, Aline de Paula Dias da Silva, Samuel Coelho Mandacaru, Emilly Caroline dos Santos Moraes, Monique R. O. Trugilho, João S. M. Gesto, Marcelo Alves Ferreira, Felipe Betoni Saraiva, Lohanna Palhinha, Remy Martins-Gonçalves, Isaclaudia Gomes Azevedo-Quintanilha, Juliana L. Abrantes, Cássia Righy, Pedro Kurtz, Hui Jiang, Hongdong Tan, Carlos Morel, Dumith Chequer Bou-Habib, Fernando A. Bozza, Patrícia T. Bozza, and Thiago Moreno L. Souza
Subjects: Microbial ecology, QR100-130
Abstract: Abstract Background Critically ill 2019 coronavirus disease (COVID-19) patients under invasive mechanical ventilation (IMV) are 10 to 40 times more likely to die than the general population. Although progression from mild to severe COVID-19 has been associated with hypoxia, uncontrolled inflammation, and coagulopathy, the mechanisms involved in the progression to severity are poorly understood. Methods The virome of tracheal aspirates (TA) from 25 COVID-19 patients under IMV was assessed through unbiased RNA sequencing (RNA-seq), and correlation analyses were conducted using available clinical data. Unbiased sequences from nasopharyngeal swabs (NS) from mild cases and TA from non-COVID patients were included in our study for further comparisons. Results We found higher levels and differential expression of human endogenous retrovirus K (HERV-K) genes in TA from critically ill and deceased patients when comparing nasopharyngeal swabs from mild cases to TA from non-COVID patients. In critically ill patients, higher HERV-K levels were associated with early mortality (within 14 days of diagnosis) in the intensive care unit. Increased HERV-K expression in deceased patients was associated with IL-17-related inflammation, monocyte activation, and an increased consumption of clotting/fibrinolysis factors. Moreover, increased HERV-K expression was detected in human primary monocytes from healthy donors after experimental SARS-CoV-2 infection in vitro. Conclusion Our data implicate the levels of HERV-K transcripts in the physiopathology of COVID-19 in the respiratory tract of patients under invasive mechanical ventilation. Video abstract
Published: 2022
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25. Platelet–leukocyte interactions in the pathogenesis of viral infections

Author: Eugenio D. Hottz, Anna Cecíllia Quirino-Teixeira, Laura Botelho Merij, Mariana Brandi Mendonça Pinheiro, Stephane Vicente Rozini, Fernando A. Bozza, and Patrícia T. Bozza
Subjects: platelets, platelet-leukocyte aggregates, covid-19, dengue, hiv, influenza, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Evolving evidence demonstrates that platelets have major roles in viral syndromes through previously unrecognized viral sensing and effector functions. Activated platelets and increased platelet-leukocyte aggregates are observed in clinical and experimental viral infections. The mechanisms and outcomes of platelet–leukocyte interactions depend on the interacting leukocyte as well as on the pathogen and pathological conditions. In this review, we discuss the mechanisms involved in platelet interactions with leukocytes and its functions during viral infections. We focus on the contributions of human platelet–leukocyte interactions to pathophysiological and protective responses during viral infections of major global health relevance, including acquired immunodeficiency syndrome (AIDS), dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), influenza pneumonia, and COVID-19.
Published: 2022
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26. Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture

Author: Xuanting Wang, Carolina Q. Sacramento, Steffen Jockusch, Otávio Augusto Chaves, Chuanjuan Tao, Natalia Fintelman-Rodrigues, Minchen Chien, Jairo R. Temerozo, Xiaoxu Li, Shiv Kumar, Wei Xie, Dinshaw J. Patel, Cindy Meyer, Aitor Garzia, Thomas Tuschl, Patrícia T. Bozza, James J. Russo, Thiago Moreno L. Souza, and Jingyue Ju
Subjects: Biology (General), QH301-705.5
Abstract: In this paper, the hepatitis C virus inhibitors Pibrentasvir and Ombitasvir are found to inhibit the SARS-CoV-2 exonuclease and are shown to have therapeutic potential when combined with SARS-CoV-2 polymerase inhibitors in viral cell cultures.
Published: 2022
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27. Severe influenza infection is associated with inflammatory programmed cell death in infected macrophages

Author: André C. Ferreira, Carolina Q. Sacramento, Filipe S. Pereira-Dutra, Natália Fintelman-Rodrigues, Priscila P. Silva, Mayara Mattos, Caroline S. de Freitas, Andressa Marttorelli, Gabrielle R. de Melo, Mariana M. Campos, Isaclaudia G. Azevedo-Quintanilha, Aluana S. Carlos, João Vítor Emídio, Cristiana C. Garcia, Patrícia T. Bozza, Fernando A. Bozza, and Thiago M. L. Souza
Subjects: influenza virus, necroptosis, TNF, etanercept, macrophages, Microbiology, QR1-502
Abstract: IntroductionInfluenza A virus (IAV) is one of the leading causes of respiratory tract infections in humans, representing a major public health concern. The various types of cell death have a crucial role in IAV pathogenesis because this virus may trigger both apoptosis and necroptosis in airway epithelial cells in parallel. Macrophages play an important role in the clearance of virus particles, priming the adaptive immune response in influenza. However, the contribution of macrophage death to pathogenesis of IAV infection remains unclear.MethodsIn this work, we investigated IAV-induced macrophage death, along with potential therapeutic intervention. We conducted in vitro and in vivo experiments to evaluate the mechanism and the contribution of macrophages death to the inflammatory response induced by IAV infection.ResultsWe found that IAV or its surface glycoprotein hemagglutinin (HA) triggers inflammatory programmed cell death in human and murine macrophages in a Toll-like receptor-4 (TLR4)- and TNF-dependent manner. Anti-TNF treatment in vivo with the clinically approved drug etanercept prevented the engagement of the necroptotic loop and mouse mortality. Etanercept impaired the IAV-induced proinflammatory cytokine storm and lung injury.ConclusionIn summary, we demonstrated a positive feedback loop of events that led to necroptosis and exacerbated inflammation in IAV-infected macrophages. Our results highlight an additional mechanism involved in severe influenza that could be attenuated with clinically available therapies.
Published: 2023
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28. Dengue induces iNOS expression and nitric oxide synthesis in platelets through IL-1R

Author: Mariana Brandi Mendonça Pinheiro, Stephane Vicente Rozini, Anna Cecíllia Quirino-Teixeira, Giselle Barbosa-Lima, Juliana F. Lopes, Carolina Q. Sacramento, Fernando A. Bozza, Patrícia T. Bozza, and Eugenio D. Hottz
Subjects: platelets, nitric oxide, iNOS, IL-1R, dengue, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionDengue is an arthropod-born disease caused by dengue virus (DENV), that may manifest as a mild illness or severe form, characterized by hemorrhagic fever and shock. Nitric oxide (NO) is a vasodilator signaling molecule and an inhibitor of platelet aggregation known to be increased in platelets from dengue patients. However, the mechanisms underlying NO synthesis by platelets during dengue are not yet elucidated. IL-1β is a pro-inflammatory cytokine able to induce iNOS expression in leukocytes and present in dengue patients at high levels. Nevertheless, the role of IL-1β in platelet activation, especially regarding iNOS expression, are not clear.MethodsWe prospectively followed a cohort of 28 dengue-infected patients to study NO synthesis in platelets and its relationship with disease outcomes. We used in vitro infection and stimulation models to gain insights on the mechanisms.Results and DiscussionWe confirmed that platelets from dengue patients express iNOS and produce higher levels of NO during the acute phase compared to healthy volunteers, returning to normal levels after recovery. Platelet NO production during acute dengue infection was associated with the presence of warning signs, hypoalbuminemia and hemorrhagic manifestations, suggesting a role in dengue pathophysiology. By investigating the mechanisms, we evidenced increased iNOS expression in platelets stimulated with dengue patients´ plasma, indicating induction by circulating inflammatory mediators. We then investigated possible factors able to induce platelet iNOS expression and observed higher levels of IL-1β in plasma from patients with dengue, which were correlated with NO production by platelets. Since platelets can synthesize and respond to IL-1β, we investigated whether IL-1β induces iNOS expression and NO synthesis in platelets. We observed that recombinant human IL-1β enhanced iNOS expression and dose-dependently increased NO synthesis by platelets. Finally, platelet infection with DENV in vitro induced iNOS expression and NO production, besides the secretion of both IL-1α and IL-1β. Importantly, treatment with IL-1 receptor antagonist or a combination of anti-IL-1α and anti-IL-1β antibodies prevented DENV-induced iNOS expression and NO synthesis. Our data show that DENV induces iNOS expression and NO production in platelets through mechanisms depending on IL-1 receptor signaling.
Published: 2022
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29. Contributors

Author: David Abraham, Seema S. Aceves, Steven J. Ackerman, Darryl Adamko, Koichi Akashi, Praveen Akuthota, Rafeul Alam, Judith A. Appleton, Narcy Arizmendi, Kewal Asosingh, Keir M. Balla, Christianne Bandeira-Melo, Marc Bartoli, Fleur Samantha Benghiat, Claudia Berek, Utibe Bickham, Elizabeth R. Bivins-Smith, Carine Blanchard, Bruce S. Bochner, Apostolos Bossios, Patricia T. Bozza, David Broide, Miranda Buitenhuis, William W. Busse, Joseph H. Butterfield, Jose A. Cancelas, Monique Capron, Lars Olaf Cardell, Van T. Chu, Michael R. Comeau, Joan M. Cook-Mills, Jan Cools, Olga V. Cravetchi, Benjamin P. Davis, Judah A. Denburg, Joseph B. Domachowske, Virginie Driss, Jian Du, Ann M. Dvorak, Kimberly D. Dyer, Moran Elishmereni, Michael J. Eppihimer, Serpil C. Erzurum, Gary W. Falk, Sophie Fillon, Claudio Fiocchi, Paul S. Foster, Allison D. Fryer, Glenn T. Furuta, Gail M. Gauvreau, Nebiat G. Gebreselassie, Erwin W. Gelfand, Katrin Gentil, Gerald J. Gleich, Pranab Haldar, Noriyasu Hirasawa, Achim Hoerauf, Simon P. Hogan, Ramses Ilarraza, Charles G. Irvin, Kenji Ishihara, Hiromi Iwasaki, Elizabeth A. Jacobsen, David B. Jacoby, Harsha H. Kariyawasam, Atsushi Kato, Howard R. Katz, A. Barry Kay, Elizabeth A. Kelly, Robert Kern, Paneez Khoury, Hirohito Kita, Amy D. Klion, Leo Koenderman, Roland Kolbeck, Martin Krahn, Paige Lacy, Mark C. Lavigne, Laura E. Layland, Alain Le Moine, James J. Lee, Nancy A. Lee, Fanny Legrand, Philippe Lemaitre, Séverine Letuve, Francesca Levi-Schaffer, Nicolas Levy, Ramin Lotfi, Jan Lötvall, Michael Thomas Lotze, Michael P. McGarry, Kelly M. McNagny, Salahaddin Mahmudi-Azer, Steven Maltby, James S. Malter, Anne M. Månsson Kvarnhammar, Annick Massart, Joanne C. Masterson, Kenji Matsumoto, Joerg Mattes, Rossana C.N. Melo, Nestor A. Molfino, Redwan Moqbel, Yasuo Mori, Ariel Munitz, Parameswaran Nair, Josiane Sabbadini Neves, Thomas B. Nutman, Sergei I. Ochkur, S.O. (Wole) Odemuyiwa, Kazuo Ohuchi, Kanami Orihara, Ian D. Pavord, Caroline M. Percopo, Maximilian Plank, Marina Pretolani, Calman Prussin, Catherine Ptaschinski, Madeleine Rådinger, Savita P. Rao, Florian Rieder, Douglas S. Robinson, Helene F. Rosenberg, Marc E. Rothenberg, Florence Roufosse, Robert P. Schleimer, Shauna Schroeder, Gregory D. Scott, Darren W. Sexton, Mi-Kyung Shin, Dagmar Simon, Hans-Uwe Simon, Dirk E. Smith, Neal Spada, Lisa A. Spencer, P. Sriramarao, Alex Straumann, Kiyoshi Takatsu, Anastasya Teplinsky, Alex Thomas, David Traver, Meri K. Tulic, Per Venge, Amanda Waddell, Lori A. Wagner, Garry M. Walsh, Haibin Wang, Andrew J. Wardlaw, Peter F. Weller, Christine Wennerås, Jason J. Xenakis, Yoshiyuki Yamada, Shida Yousefi, Xiang Zhu, and Nives Zimmermann
Published: 2013

30. Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19

Author: Marcos C. Gama-Almeida, Gabriela D. A. Pinto, Lívia Teixeira, Eugenio D. Hottz, Paula Ivens, Hygor Ribeiro, Rafael Garrett, Alexandre G. Torres, Talita I. A. Carneiro, Bianca de O. Barbalho, Christian Ludwig, Claudio J. Struchiner, Iranaia Assunção-Miranda, Ana Paula C. Valente, Fernando A. Bozza, Patrícia T. Bozza, Gilson C. dos Santos, and Tatiana El-Bacha
Subjects: SARS-CoV-2, metabolomics, 1H-NMR, high-resolution mass spectrometry, fatal COVID-19, virus-host interactions, Microbiology, QR1-502
Abstract: Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients’ sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.
Published: 2023
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31. Modulation of lipid droplets by Mycobacterium leprae in Schwann cells: a putative mechanism for host lipid acquisition and bacterial survival in phagosomes

Author: Katherine A, Mattos, Flavio A, Lara, Viviane G C, Oliveira, Luciana S, Rodrigues, Heloisa, D'Avila, Rossana C N, Melo, Pedro P A, Manso, Euzenir N, Sarno, Patricia T, Bozza, and Maria Cristina V, Pessolani
Subjects: Cytoplasm, Microscopy, Microbial Viability, Membrane Proteins, Lipid Metabolism, Immunohistochemistry, Perilipin-2, Mycobacterium leprae, Phosphatidylinositol 3-Kinases, Phagosomes, Humans, Schwann Cells, Cells, Cultured, Cytoskeleton, Signal Transduction
Abstract: The predilection of Mycobacterium leprae (ML) for Schwann cells (SCs) leads to peripheral neuropathy, a major concern in leprosy. Highly infected SCs in lepromatous leprosy nerves show a foamy, lipid-laden appearance; but the origin and nature of these lipids, as well as their role in leprosy, have remained unclear. The data presented show that ML has a pronounced effect on host-cell lipid homeostasis through regulation of lipid droplet (lipid bodies, LD) biogenesis and intracellular distribution. Electron microscopy and immunohistochemical analysis of lepromatous leprosy nerves for adipose differentiation-related protein expression, a classical LD marker, revealed accumulating LDs in close association to ML in infected SCs. The capacity of ML to induce LD formation was confirmed in in vitro studies with human SCs. Moreover, via confocal and live-cell analysis, it was found that LDs are promptly recruited to bacterial phagosomes and that this process depends on cytoskeletal reorganization and PI3K signalling. ML-induced LD biogenesis and recruitment were found to be independent of TLR2 bacterial sensing. Notably, LD recruitment impairment by cytoskeleton drugs decreased intracellular bacterial survival. Altogether, our data revealed SC lipid accumulation in ML-containing phagosomes, which may represent a fundamental aspect of bacterial pathogenesis in the nerve.
Published: 2010

32. Cross-talk between macrophage migration inhibitory factor and eotaxin in allergic eosinophil activation forms leukotriene C₄-synthesizing lipid bodies

Author: Adriana, Vieira-de-Abreu, Andrea S, Calheiros, Fabio P, Mesquita-Santos, Elisabeth S, Magalhães, Diego, Mourão-Sá, Hugo C, Castro-Faria-Neto, Marcelo T, Bozza, Christianne, Bandeira-Melo, and Patricia T, Bozza
Subjects: Chemokine CCL11, Inclusion Bodies, Lipopolysaccharides, Histocompatibility Antigens Class II, Models, Immunological, Pneumonia, Lipid Metabolism, Leukotriene C4, Antigens, Differentiation, B-Lymphocyte, Eosinophils, Intramolecular Oxidoreductases, Mice, Cell Movement, Hypersensitivity, Animals, Humans, Macrophage Migration-Inhibitory Factors
Abstract: Recent studies have demonstrated an essential and nonredundant role for macrophage migration inhibitory factor (MIF) in asthma pathogenesis. Here we investigate the mechanisms involved in MIF-induced eosinophil activation. By using a model of allergic pulmonary inflammation, we observed that allergen challenge-elicited eosinophil influx, lipid body (also known as lipid droplets) biogenesis, and leukotriene (LT) C₄ synthesis are markedly reduced in Mif(-/-) compared with wild-type mice. Likewise, in vivo administration of MIF induced formation of new lipid bodies within eosinophils recruited to the inflammatory reaction site that corresponded to the intracellular compartment of increased LTC₄ synthesis. MIF-mediated eosinophil activation was at least in part due to a direct effect on eosinophils, because MIF was able to elicit lipid body assembly within human eosinophils in vitro, a phenomenon that was blocked by neutralization of the MIF receptor, CD74. MIF-induced eosinophil lipid body biogenesis, both in vivo and in vitro, was dependent on the cooperation of MIF and eotaxin acting in a positive-feedback loop, because anti-eotaxin and anti-CCR3 antibodies inhibit MIF-elicited lipid body formation, whereas eotaxin-induced lipid body formation is affected by anti-CD74 and MIF expression deficiency. Therefore, allergy-elicited inflammatory MIF acts in concert with eotaxin as a key activator of eosinophils to form LTC₄-synthesizing lipid bodies via cross-talk between CD74 and CCR3. Due to the effect of MIF on eosinophils, strategies that inhibit MIF activity might be of therapeutic value in controlling allergic inflammation.
Published: 2010

33. PFO

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

34. PRPP Synthetase Superactivity

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

35. Pyoderma Gangrenosum

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

36. Poly- and Dermatomyositis

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

37. Parasternal Chondrodynia

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

38. Purpura Rheumatica

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

39. Puna Soroche

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

40. Primary Systemic Carnitine Deficiency

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

41. Pancreatitis, Autoimmune

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

42. Pure Cutaneous Histiocytosis

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

43. Polyneuropathy, Chronic Inflammatory Demyelinating

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

44. Persistent Atrioventricular Ostium

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

45. Primary (Congenital) Intestinal Lymphangiectasia

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

46. Primary Carnitine Deficiency

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

47. Primary Sclerosing Cholangitis

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

48. Pulmonary Hypertension

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

49. Phosphorylase B Kinase Deficiency

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

50. Primary Open Angle Glaucoma

Author: Markus Braun-Falco, Henry J. Mankin, Sharon L. Wenger, Stephan DiSean Kendall, Gerard C. Blobe, Christoph K. Weber, Richard Lorenz, Guido Adler, David C. Whitcomb, Dhiraj Yadav, Johannes Bode, Martin Wabitsch, Klaus-Michael Debatin, Pamela Fischer Posovzsky, Akmal Hassan, Mosaad Megahed, Tord M. Lundgren, Markus Pfister, Hans-Peter Zenner, Rossana Berardi, Chiara Pierantoni, Mario Scartozzi, Stefano Cascinu, Geoffrey N. Hendy, Johannes Schwarz, Alexander Storch, John-John B. Schnog, Victor E. A. Gerdes, Susanne A. Schneider, Kailash P. Bhatia, Adriana C. Gittenberger-de Groot, Regina Bökenkamp, Marco C. DeRuiter, Alexander K. C. Leung, Andrew L. Wong, Undine E. Lang, Muammer Seyhan, Silke Hofmann, Leena Bruckner-Tuderman, Peter Kopp, Douglas Forrest, Emine Dibek Misirlioğlu, Nursel Alpan, Mark Oette, Massimo Imazio, Kavitha M. Chinnaiyan, Laxmi S. Mehta, Mushtaq A. Bhat, Javeed I. Bhat, Gerald Stöber, André Reis, Jan Rémi, Soheyl Noachtar, Karin Jurkat-Rott, Frank Lehmann-Horn, Marinella Holzhausen, Nathalie Vergnolle, Martin Schillinger, Hans-Jürgen Gdynia, Albert C. Ludolph, Thomas Namdar, Claus Ferdinand Eisenberger, Wolfram Trudo Knoefel, Pere Ginés, Mónica Guevara, Antonio L. Cuesta-Muñoz, Henk Eijer, Markus Böhm, Thomas A. Luger, Flemming Güttler, Per Guldberg, Richard Koch, Kathryn Moseley, Graeme Eisenhofer, Karel Pacak, James V. Leonard, Jaak Jaeken, Michael A. Becker, Ulrich Stephani, Kendall S. Frazier, Reginald S. Sauve, Verena Matejas, Martin Zenker, William Lane M. Robson, Stefan Beissert, Tom Y. Woo, Hugo Ten Cate, Richard W. Light, Patricia T. Bozza, Jorge I. Salluh, Michael A. Jantz, Sergio L. Vargas, Rade Tomic, Jesse Roman, Abdullah F. Mobeireek, Mohammad Khalid, Harrys A. Torres, Roy F. Chemaly, Angela Dispenzieri, Sabine Krause, Hanns Lochmüller, Julia Weihrauch, Thomas Krieg, Wolfgang Kühn, Gerd Walz, Georg H. Merker, Ralf Kubitz, Dieter Häussinger, Giovanna Musco, Guido Stoll, Klaus V. Toyka, Elena Pischik, Raili Kauppinen, Jorge Frank, Thomas Schwarz, Manish Thapar, Herbert. L. Bonkovsky, Jeffrey C. Wagner, A. Gordon Smith, Maria Mela, Ulrich Thalheimer, Dimitrios Samonakis, Andrew K. Burroughs, Yogesh M. Shastri, Jürgen M. Stein, Ronnen H. Segman, Arieh Y. Shalev, Giris Jacob, David Robertson, Katja Lampinen, Karolina Kublickiene, Risto Kaaja, Radosław Lenarczyk, Oskar Kowalski, Zbigniew Kalarus, Dan Wichterle, Jamie Maguire, Istvan Mody, Katrien Janssens, Filip Vanhoenacker, Wim Van Hul, Karel Geboes, Gert Van Assche, Jo H. M. Berden, Toin H. Van Kuppevelt, Angelique L. Rops, Christina M. Ambros-Rudolph, Valéria Lamounier-Zepter, Christie P. Thomas, Christian A. Koch, Lee S. Weinstein, Caroline Silve, Jouni Uitto, Qiujie Jiang, Orhan Yildiz, Uner Kayabas, Richard G. Hegele, Jean-Nicolas Tournier, Ahmet Mesrur Halefoğlu, Mary Redmond Hutson, Margaret L. Kirby, Fumito Okada, Yumiko Ando, Asami Ono, Hiromu Mori, Timothy M. Moore, Mary I. Townsley, Maria-T. Krauth, Ingrid Pabinger, Manfred Ballmann, Terence K. Trow, Vallerie V. McLaughlin, Atteyet-Alla Fetouh Yassin, Anselm Uebing, Michael A. Gatzoulis, Helena M. Gardiner, Lucia K. Ma, Patrick T. S. Ma, Lourdes Prieto, Larry Latson, Nancy R. Keller, Lynette D. Fairbanks, H. Anne Simmonds, Martina Brunner, Christos C. Zouboulis, Vincent Everts, Miep Helfrich, Peter Von Den Driesch, Roland Bitsch, Angels García-Cazorla, and Jean Marie Saudubray
Published: 2009

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